The objectives of the Northern California Comprehensive Sickle Cell Center (NCCSCC) are:1) to facilitate hemoglobinopathy research in the areas of basic research, clinical science, psychosocial aspects of the disease;and to initiate multicenter collaborative research projects 2) to provide hemoglobinopathy detection, counseling, education and care to affected populations. To pursue these objectives, we have developed interdependent basic research programs at Childrens'Hospital Oakland Research Institute (CHORI) and University of California at San Francisco (UCSF). These basic programs are complemented by core clinical research programs in the West Bay (UCSF/San Francisco General Hospital) and in the East Bay (Childrens'Hospital Oakland]. These programs provide hemoglobinopathy detection, counseling, education and comprehensive care needed to maintain a stable, well characterized group of over 700 patients with sickle cell disease (SCD) who participate in NCCSCC research projects. Clinical, basic and collaborative network research projects aims are: A) To initiate a phase lla, randomized, trial to determine if LY315920 [anti PLA 2 inhibitor] can be safely used to prevent impending ACS and to characterize the mechanisms by which it prevents damage. B) To determine the extent of neurocognitve and neuromimaging abnormalities in neurologically asymtomatic adult SCD patients. C) To understand the mechanisms that result in phospholipid asymmetry in red cell membranes and to determine their in vivo significance in SCD patients by studying physiological processes. D) To construct sickle cell mice utilizing BAC's to isolate the beta-globin clusters from patients with the four sickle haplotypes: Benin, CAR, Senegal and Saudi Arabia, and to study their pathophysiology and rheology. E) Our network project's aim is to test hypothesis that a non-myeloablative conditioning regimen in young adults with symptomatic SCD a can induce stable donor host hematopoietic chimerism after stem cell transplantation from HLA identical sibling donors.